Extracellular protease imaging for cell mass tracking of xenografted human malignant pleural mesothelioma

Our plain-English summary of Extracellular protease imaging for cell mass tracking of xenografted human malignant pleural mesothelioma, by L. Zhou, W. El-Deiry, W. Wang, et al (Oncology Reports, 2012).

The study

• Authors: L. Zhou, W. El-Deiry, W. Wang, M.E. Ingram, S.I. Katz
• Journal: Oncology Reports
• Published: 2012;28(3):883-8
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is locally aggressive and challenging to quantitate non-invasively in vivo, particularly in orthotopic models of disease. We describe imaging of extracellular protease activity, typically elevated in locally aggressive tumors, as a novel method for tracking MPM in vivo. Mice bearing human MPM subcutaneous flank xenografted tumors were imaged with ProSense 680, an optical imaging agent of extracellular cysteine protease activity. The relative contribution of extracellular cysteine proteases to the ProSense tumor signal was estimated using RT-PCR quantitation of cysteine protease RNA expression of the MPM cell lines and compared to ArrayExpress microarray RNA expression data from human MPM tumors. Feasibility of orthotopic intraperitoneal MPM cell mass tracking with fluorescence signal was evaluated using CellVue Maroon-coated MSTO-211H and compared to bioluminescent signal using luciferase-transfected MSTO-211H cells. ProSense 680 yielded a robust tumor signal in MPM subcutaneous grafts, primarily resulting from MPM secretion of cathepsin L demonstrated not only by RT-PCR data on MPM cell lines but also by microarray expression data from resected human patient tumors. CellVue Maroon intraperitoneal tumor signal was robust and durable indicating feasibility of intraperitoneal cell mass tracking of orthotopically-xenografted MPM. Optical imaging of extracellular cysteine protease activity is useful for tracking MPM tumor cell mass in vivo. Intraperitoneal MPM cell mass tracking of fluorescently labeled tumor is feasible.

In plain English

This mouse and laboratory study tested ways to follow human malignant pleural mesothelioma tumors grown in mice. It did not study asbestos exposure. The authors placed human mesothelioma cells in immunocompromised mice, either under the skin of the flank or into the abdominal (intraperitoneal) cavity. In the flank tumors, an imaging agent called ProSense 680, which glows when cut by enzymes called proteases, gave a strong signal still detectable up to 3 weeks after injection. Tests of five mesothelioma cell lines showed that the signal was likely mainly the result of one enzyme, cathepsin L. The authors also analyzed public data on 12 human tissue samples (5 mesothelioma, 6 normal pleura, 1 pleural plaque). Cathepsin L was more than 2-fold higher in mesothelioma than in normal pleura or pleural plaque. Cells coated with a dye, CellVue Maroon, were tracked in the abdomen for 3 weeks, though their signal was weaker than that of luciferase-labeled cells. The authors concluded that protease imaging, tested in flank tumors, is useful for tracking these tumors in mice, and that dye-based tracking in the abdomen is feasible. They said a quantitative study is still needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Experimental mouse xenograft imaging study, combined with RT-PCR of mesothelioma cell lines and analysis of publicly available human tissue microarray data
• Who was studied: Immunocompromised female nu/nu mice (number not stated) given grafts of human MPM cell lines; five MPM cell lines (H28, H2052, M30, MSTO-211H, H2452); 12 human tissue samples from the ArrayExpress database: 6 visceral pleura, 5 malignant pleural mesothelioma, 1 benign pleural plaque
• Exposure: No asbestos exposure was studied. The study tested imaging agents: ProSense 680 (a protease-activated fluorescent probe) in subcutaneous flank tumors, CellVue Maroon cell-surface dye in flank and intraperitoneal tumors, and luciferase-transfected MSTO-211H cells for comparison
• Main results:
  • In the mouse mesothelioma flank grafts, ProSense 680 signal remained detectable up to 3 weeks after injection
  • In the 5 MPM cell lines, only very low levels of other proteases were found and no cathepsin B or S. The authors judged the tumor signal likely primarily due to cathepsin L, which was highest in H28 and lowest in M30
  • In the human tissue data, cathepsin L was elevated more than 2-fold in MPM, but not in normal pleura or pleural plaque
  • CellVue Maroon-labeled MSTO-211H cells were tracked for 3 weeks after grafting, with a weaker signal than bioluminescence
  • At necropsy, the CellVue signal matched where the tumor cell masses were, in both flank and intraperitoneal sites, after 3 weeks
• The authors' conclusion: The authors concluded that optical imaging of extracellular protease activity (ProSense 680, tested in subcutaneous flank grafts) is useful for tracking MPM tumor cell mass in mice, and that intraperitoneal tracking of fluorescently labeled tumor is feasible
• Limitations the authors state:
  • The long-lasting ProSense 680 signal limits which other imaging agents can be given at the same time or afterward
  • Cell-surface dye labeling may lose its label when drugs are given into the abdomen, and may interfere with other fluorescent tracers given by vein
  • Luciferase imaging has its own caveats, including the stability of transfection and its dependence on substrate injection
  • Intraperitoneal tracking was assessed qualitatively, and a quantitative study is still needed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma.

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